Criteria for the control of drug-resistant tuberculosis

Antibiotic resistance is a growing impediment to the control of infectious diseases worldwide, tuberculosis (TB) being among them. TB kills two million people each year and foci of multidrug-resistant TB (MDR-TB) have been identified in Eastern Europe, Africa, Asia, and Latin America. A critical question for health policy is whether standardized short-course chemotherapy for TB, based on cheap first-line drugs, can prevent and reverse the spread of drug resistance. Here we use mathematical modeling, in conjunction with treatment results from six countries, to show that best-practice short-course chemotherapy is highly likely to bring strains resistant to either of the two key drugs isoniazid and rifampicin under control and to prevent the emergence of MDR-TB. However, it is not certain to contain MDR-TB once it has emerged, partly because cure rates are too low. We estimate that approximately 70% of prevalent, infectious MDR-TB cases should be detected and treated each year, and at least 80% of these cases should be cured, in order to prevent outbreaks of MDR-TB. Poor control programs should aim to increase case detection and cure rates together for three reasons: (i) these variables act synergistically; (ii) when either is low, the other cannot succeed alone; and (iii) the second-line drugs needed to raise MDR-TB cure rates are few and extremely costly. We discuss the implications of these results for World Health Organization policy on the management of antibiotic resistance.

抗生素耐药性已成为全球传染病防控领域日益严峻的阻碍，结核病（Tuberculosis, TB）正是受其影响的传染病之一。结核病每年造成200万人死亡，且耐多药结核病（Multidrug-resistant TB, MDR-TB）的传播焦点已在东欧、非洲、亚洲及拉丁美洲被确认。卫生政策领域的核心问题在于，基于廉价一线药物的标准化结核病短程化疗方案，能否预防并扭转耐药性的传播态势。本研究结合六国的临床治疗结果，通过数学建模证实：规范实施的短程化疗极有可能控制对两种关键药物——异烟肼（Isoniazid）与利福平（Rifampicin）——任一产生耐药性的结核菌株，并遏制耐多药结核病的出现。然而，一旦耐多药结核病已出现，该方案未必能够遏制其扩散，部分原因在于治愈率过低。经估算，若要防范耐多药结核病暴发，每年需检出并治疗约70%的现存传染性耐多药结核病病例，且其中至少80%的病例应得到治愈。防控效能不佳的项目应致力于同时提升病例检出率与治愈率，原因有三：其一，两项指标存在协同增效作用；其二，若任一指标处于低位，仅凭另一项无法达成防控目标；其三，用于提升耐多药结核病治愈率的二线药物数量稀少且成本极其高昂。本研究还探讨了上述结论对世界卫生组织（World Health Organization）抗生素耐药性管理政策的影响。